Michael G. McDonell, Ph.D. - US grants

DESCRIPTION (provided by applicant): Novel EtG Based Contingency Management for Alcohol in the Severely Mentally Ill We propose to conduct a randomized clinical trial investigating the effect of a 12-week ethyl glucuronide (EtG) urinalysis based contingency management (CM) intervention on decreasing alcohol use and increasing alcohol treatment attendance among persons with alcohol dependence (AD) and serious mental illness (SMI) receiving long-term community mental health treatment. While CM is an evidence-based treatment for illicit drug use, research regarding its efficacy for AD has been limited due to the absence of a pragmatic alcohol biomarker to base the CM paradigm upon. This study will include the novel application of EtG urine-tests, capable of detecting alcohol use for a two-day period similar to urine-tests of illicit drug use, on which most CM drug research has been based. EtG results will be utilized as both a research outcome and as a basis on which the CM intervention targeting alcohol use is based. In addition, the CM paradigm will include secondary reinforcement of attendance in intensive outpatient (IOP) addiction treatment. It is hypothesized that this secondary contingency will result in higher rates of IOP attendance. 120 AD-SMI adults will participate in a 4-week induction period (reinforcement for providing urinalysis three times a week). All participants will receive treatment as usual (TAU) for SMI and intensive outpatient (IOP) addiction treatment throughout the study. After an induction period participants will be randomized to receive either 1) 12 weeks of CM for alcohol abstinence (assessed 3 times a week by EtG urine-tests) AND weekly reinforcement for IOP addiction treatment attendance; or 2) 12 weeks of reinforcement for providing urine-tests 3 times a week. The primary outcome will be changes in alcohol use assessed by EtG urinalysis, breathalyzer, as well as self-reported and clinician-reported alcohol use. The secondary outcome will be changes in IOP addiction treatment attendance assessed by IOP clinician-report, as well as independent administrative data sources, and self-report. Other outcomes will include: biological measures of illicit drug use, self-reported illicit drug use, psychiatric symptoms, HIV-risk, nicotine use, and utilization f costly emergency department, inpatient psychiatric and residential addiction treatment services. All outcomes will be assessed across the 12-week intervention and a 3-month follow-up period. This proposed study addresses two public health priorities--alcohol use and poor treatment attendance--in a population of adults with SMI for whom these difficulties are especially prevalent and problematic; and is responsive to NIAAA PA-10-100, Alcohol Use Disorders: Treatment, Services Research, and Recovery (R01).

PROJECT SUMMARY/ABSTRACT A high prevalence of alcohol dependence, compounded by a lack of culturally acceptable treatment options, is one of the most severe health disparities faced by American Indians and Alaska Natives (AI/AN). AI/ANs suffer disproportionately from alcohol dependence and its medical and psychosocial consequences relative to other racial and ethnic groups. AI/ANs are also less likely to receive or complete alcohol treatment relative to Whites. Some treatments for alcohol dependence are effective in non-Native populations, yet little is known about their acceptability and benefit for AI/ANs. One approach to reducing alcohol-associated health disparities is to form partnerships between AI/AN communities, clinicians, and researchers to tailor and test treatments in AI/ANs that have established benefits for other groups. This approach holds promise for developing treatments that are culturally acceptable, effective, sustainable, and portable. Contingency management (CM) is an intervention that offers rewards 2-3 times weekly for drug or alcohol abstinence, typically over 12 weeks of treatment. In non-AI/AN populations, CM is one of the most effective and well-studied behavioral treatments for illicit drug abuse. Compared to standard care, CM has higher rates of 8-week in-treatment abstinence (58% vs. 11%), 12-month post-treatment abstinence (30% vs. 5%), and treatment completion (75% vs. 40%). However, few studies have examined CM for alcohol dependence, primarily because of the lack of a biomarker that can detect alcohol use over more than 2 days (a requirement for CM). We have overcome this critical methodological barrier by using a new and superior measure of recent alcohol consumption, namely, ethyl glucuronide urine tests, which can detect low levels of alcohol use for at least the past 2 days. This approach permits us to implement and accurately evaluate CM for alcohol dependence in AI/AN adults. We propose to conduct a randomized, controlled trial of a culturally-acceptable CM intervention to encourage and support abstinence among AIs from 3 tribes living on 2 reservations and AI/ANs receiving services at an urban Indian healthcare facility. After we utilize qualitative research methods to modify the CM protocol to maximize cultural acceptability in each community, 400 individuals with alcohol dependence will receive treatment-as-usual and take part in a 4-week induction period before randomization either to an intervention consisting of 12 weeks of CM, or to a control condition of treatment as usual and non- contingent rewards. Our specific aims are to 1) maximize the cultural acceptability of the CM intervention; 2) determine if participants randomized to the CM group use less alcohol than those in the control group; 2) quantify group differences in secondary addiction-related outcomes and alcohol-associated health-impairing behaviors; and 3) identify demographic, cultural, and other predictors of treatment outcome in the CM group. Our results will offer definitive evidence on the efficacy of CM as a treatment for alcohol dependence in urban and rural AI/AN populations and build the research and clinical infrastructure of our community partners.

ABSTRACT The objective of this competing continuation (renewal) application is to determine whether modifications to a contingency management (CM) intervention improve outcomes and reduce costs in heavy drinkers with serious mental illness (SMI). Up to 46% of adults with SMI experience an alcohol use disorder in their lifetimes. Alcohol use contributes to high rates of homelessness, psychiatric hospitalization, HIV infection, cigarette smoking, and drug use in this population, for which CM is an especially promising treatment. In CM, patients receive tangible rewards for demonstrating drug abstinence. CM for alcohol use requires a biomarker that can detect alcohol use for more than 48 hours after consumption. As no such biomarker was available until recently, little research has investigated CM as a treatment for alcohol use disorders. In our initial funding period we found that the alcohol biomarker ethyl glucuronide (EtG) can detect drinking for up to 5 days when administered as part of a randomized 12-week trial of CM. Those randomized to EtG-based CM were 3 times more likely to submit alcohol-negative EtG tests than controls. CM participants also had lower levels of heavy drinking, stimulant drug use, and cigarette smoking than controls. However, CM was ineffective for participants with an average pre-treatment EtG level that indicated frequent, recent heavy drinking (EtG > 499 ng/mL). We propose to investigate whether 2 strategies ? a) increasing reinforcer magnitude or b) reinforcing light drinking before reinforcing abstinence ? can improve outcomes in heavy drinkers with SMI. While initial research indicates that these strategies are associated with improved outcomes in treatment-resistant drug users and cigarette smokers, no randomized trial has compared them, investigated them in alcohol users or adults with SMI, investigated their relative cost-effectiveness, or investigated modifiers of CM efficacy using a theoretical model. Therefore, we will compare the efficacy of these 2 approaches to the CM intervention implemented in the initial funding period in heavy drinkers with SMI. A total of 400 participants receiving treatment as usual at 2 treatment agencies will take part in a 4-week induction period. Participants (n=240) who attain a mean EtG > 499 ng/mL during the induction period will be randomized to either a) 4 months of standard-magnitude reinforcement CM for submitting alcohol-abstinent EtG samples (EtG < 100 ng/mL) (Usual CM), b) 4 months of high-magnitude CM for submitting alcohol-abstinent EtG samples (High-Magnitude CM), or c) 1 month of CM for submitting alcohol samples that indicate light drinking (EtG < 500 ng/mL), followed by 3 months of CM for submitting alcohol-abstinent EtG samples (Shaping CM). The primary outcome will be EtG-verified alcohol abstinence during the last 3 months of treatment (when all reinforcement is contingent on abstinence) and during 6 months of follow-up. We will also investigate group differences in secondary outcomes, conduct a comprehensive economic analysis of CM conditions, and determine whether variables that make up the NIAAA Addictions Neuroclinical Assessment framework moderate alcohol abstinence in the 3 CM conditions.

PILOT PROJECT CORE ABSTRACT The goal of the Native Center for Alcohol Research and Education (NCARE) is to nurture innovative research on health inequities among American Indians and Alaska Natives (AI/ANs) due to alcohol use disorders (AUDs), including their prevention, diagnosis, treatment, and consequences across the lifespan. One critical strategy for achieving this goal is to fund pilot projects that will develop novel approaches to improving AI/AN population health. Pilot projects provide a way to seed emerging research areas, explore new methodologies, and pursue new regional and national collaborations that could evolve into independently funded research or demonstration projects. Existing university-based options for pilot funding provide limited sums (e.g., $5,000-$10,000) that are often inadequate to conduct community-based research and are typically restricted to investigators at the home institution. The Pilot Project Core of NCARE is designed to identify and allocate substantial funding to support pilot projects that rigorously test practices, treatments, educational efforts, and policies that can effect sustained, widespread reductions in AI/AN health disparities due to AUDs. We will recruit a broad range of investigators from NCARE and outside institutions who can begin or augment their research with support from the Pilot Project Core. Given serious concerns about the aging of the scientific workforce funded by the National Institutes of Health, and the equally worrisome dearth of minority Principal Investigators, we will encourage applications from junior faculty and AI/AN investigators. The Pilot Project Core will offer myriad possibilities for research, including but not limited to studies of the etiology, biology, genetics, diagnosis, treatment, and prevention of AUDs and their biomedical, psychosocial, and economic consequences. Our Specific Aims are to: 1) Create a Pilot Project Core to fund innovative Pilot Projects with meaningful implications for AUDs and related health inequities in AI/AN communities; 2) Use the scientific review process as a learning opportunity for junior investigators and NCARE members who desire reviewing experience; and 3) Develop centralized research services that support the investigators who lead NCARE Pilot Projects, including junior investigators with a strong interest in alcohol research. We will also leverage our successful experience with other small grant programs to offer financial, logistical, and scientific resources to researchers whose proposals meet our rigorous criteria. By creating a centralized research support service and allocating substantial financial resources for NCARE Pilot Projects, this approach will foster an ecosystem of innovative and rigorous research. The activities of the Pilot Project Core will support investigators nationwide, thereby contributing to the development of new scientific methods, technologies, and approaches pertinent to innovative, goal-directed AUD research on a national scale.

ABSTRACT Nearly 40% of homeless adults currently struggle with an alcohol use disorder (AUD). While ?housing first? programs are increasingly available, most homeless people must refrain from alcohol use to obtain and maintain housing. Contingency management (CM) is one of the most effective behavioral interventions for initiating abstinence from alcohol and drugs. In a randomized trial of CM for AUDs in adults with co-occurring serious mental illness, 60% of whom were homeless, we found that those who received CM were 3 times more likely to submit alcohol-negative urine ethyl glucuronide tests (uEtG), relative to controls. However, homeless individuals were 8 times more likely to drop out of CM, relative to housed individuals. Therefore, CM appears to work best for those who are housed. By using CM to reduce alcohol use in formerly homeless individuals who are now housed, CM might prevent subsequent alcohol-associated homelessness. The brief periods of detection of uEtG (2-5 days) and other alcohol biomarkers require monitoring of abstinence multiple times a day (breath tests) or week (uEtG) in a CM intervention. Such frequent monitoring is not feasible in most housing programs or necessary once individuals obtain prolonged periods of abstinence. Phosphatidylethanol (PEth) is a lipid-based biomarker that can detect alcohol use for up to 28 days. The lengthy detection period of PEth would allow for a more feasible monitoring and reinforcement schedule (e.g. 1 assessment every 1 to 4 weeks) and allows for the development of a CM intervention that can reinforce maintenance of long-term abstinence (e.g., monitoring and reinforcement once every 4 weeks). We propose to assess the feasibility and initial efficacy of a PEth-based CM intervention by randomizing 50 currently housed, formerly homeless adults with AUDs receiving supported housing from Catholic Charities Spokane. Participants will be randomized to either 6 months of a) treatment-as- usual (TAU) and reinforcers for submitting blood samples, regardless of PEth results (Non-contingent Control), or b) TAU and reinforcers for PEth results consistent with abstinence (CM). They will then complete a 3-month post-intervention follow-up. Our CM intervention will include 2 phases. In the initiation phase, PEth samples will be collected and reinforcers delivered weekly until individuals attain a PEth level consistent with prolonged abstinence (i.e., PEth 16:0/18:1 <20 ng/mL). CM participants will then enter the maintenance phase where they will submit less frequent PEth samples, 1 sample every 2 to 4 weeks. In this treatment development study, we will simultaneously evaluate intervention acceptability and feasibility using quantitative and qualitative methods and initial efficacy by documenting differences in alcohol abstinence, housing tenure and alcohol associated harms. We will use the Theoretical Domains Framework to guide our assessment of factors that might influence implementation of the intervention. Results will be used to support an R01 application to conduct a multi-site hybrid effectiveness/implementation trial to determine the impact of the intervention on alcohol use, housing outcomes, and alcohol related harms, as well as assess implementation science outcomes.